"The cure for boredom is curiosity. There is no cure for curiosity." -Dorothy Parker

research

Have you heard of Tomatosphere™? This is a really cool program operated in Canada through Let’s Talk Science. It is a free program offered to students from Kindergarten to Grade 12, where these students can study the effects of “space” on the germination of tomato seeds. Participating classes receive two packages of tomato seeds: one is a package of seeds from tomatoes that were sent into space or treated to space-simulation conditions, i.e., the experimental group; the second package contains seeds that spent time on plain old Earth, i.e., the control group. Students the study the germination of these two groups of seeds, expanding on the basic experiment depending on curriculum and grade level.

As a scientist and a gardener, I am in LOVE with this program. But I have a question for Tomatosphere™: I want to know if anyone is looking at the possibility of EPIGENETIC changes to the tomatoes. This begs the next question: what is epigenetics? That’s the question I am hoping to answer for you today.

My tweet to Tomatosphere

To begin our understanding of epigenetics, let’s do a quick review of the central dogma of genetics and inheritance. The traits that make us a human (or a gorilla, or a tomato plant) are coded in our DNA. To express the trait, the DNA is transcribed into messenger RNA (mRNA), which is in turn translated into amino acids that are then put together to build the necessary proteins for each trait. We inherit these genes from our biological parents: one gene from the egg and one gene from the sperm. The trait that is expressed is the dominant gene. Differences in expression generally mean differences in the genes, or the specific DNA code.

For example, let’s look at blood types. Let’s say you inherit the “A gene” from your dad and the “O gene” from your mum. Your genotype will be AO. But since the A gene is dominant, you will only express this gene and you will have blood type A. This is called your phenotype. To change your blood type, you would need to change your genotype. That is the basics of inheritance.

Epigenetics throws a wrench into this understanding of genetics and inheritance. Epigenetics means “outside genetics”, and refers to changes in gene expression that are not a result of physical changes to the DNA sequence. In other words, changing our phenotype without changing our genotype. Epigenetic marks control the expression of genes, which ones are turned on, when, and how much. One of the most interesting things about epigenetics is that we can start to see how the environment plays a role in gene expression. Our lifestyles, our preferences, our exposures to certain environmental factors can all contribute to variations in how the same gene can be expressed across individuals. What’s more, is that it has been discovered that these changes in epigenetics can be inherited. What this means is that if you exposed to something in your environment that causes a change in how a gene in your DNA is expressed, this change could be passed on to your child, and even to your grandchild. This is referred to as transgenerational epigenetics. It is an emerging area of research and the exact mechanisms of how this works is being widely studied.

This brings us back to Tomatosphere™ and my question. In the experiment we have tomato seeds that were exposed to space conditions. These conditions may not have changed the gene sequence, the genotype, of the tomato, but they may have caused epigenetic changes. It has been shown that changes in the gene that controls ripening in tomatoes is impacted by epigenetics, so do we see changes in other factors with these space tomatoes? AND, what about the progeny? Do the tomato plants grown from the seeds of the space tomatoes also show epigenetic changes?

A sketch of my proposed Tomatosphere experiment.

For more information on transgenerational epigenetics, check out this Nature article. I also recommend the website What is Epigenetics for a more detailed description of epigenetics.

Last week, March 6th, Canada’s Liberal Party was out promoting Budget 2018. This budget has Canada’s scientific community pretty excited because of the huge investment that the Canadian government is making in fundamental research. I am no exception. So last week, the Liberal politicians were out making the rounds to promote the budget and its impact on Canadian science: there was Navdeep Bains visiting Memorial University; there was Finance Minister Bill Morneau at the Djavad Mowafaghian Centre for Brain Health and Brain Behaviour Laboratory; and there was Science Minister Kristy Duncan was over at the University of Waterloo. But all eyes were on Canada’s mascot, I mean Prime Minister, Justin Trudeau. See Trudeau did his post-budget armchair discussion at the University of Ottawa with none other than Canada’s most prominent scientist and science educator…oh no wait, he sat down with Bill Nye. That’s right, American engineer and television host, Bill F*cking Nye. This pissed me off – so much that I actually had a Twitter rant about it.

I am not one who is usually given to ranting my feelings on social media. I don’t feel that 280 characters is enough to fully express nuanced thoughts, and much of the time it feels like I am trying to talk in a room of 1000 other people all talking at the same time. But here’s my top 3 reasons why I am incredibly disappointed in the PM’s choice to have this discussion with Bill Nye:

1) Bill Nye IS NOT CANADIAN

I don’t think I can stress this enough. Bill Nye isn’t Canadian. He wasn’t born in Canada. He wasn’t educated in Canada. He never worked in Canada. He hasn’t lived in Canada. He has never paid taxes in Canada. Other than clips of Bill Nye the Science Guy showing up in Canadian science classrooms, he doesn’t have a Canadian connection. He is simply not a stakeholder in Canadian federal budgets.

It is deeply disappointing that of the THOUSANDS of Canadian scientists, myself included, that would have happily discussed the benefits of investing in STEM and research, that of the THOUSANDS of Canadian scientists who could have connected to Canadian taxpayers why it is so important for the government to spend their money on research and innovation even if they themselves aren’t scientists, the Canadian Prime Minister chose an American. Trudeau took away an opportunity for a Canadian voice to be on that platform. He allowed an American, someone who doesn’t benefit from the budget, and doesn’t have to answer to the consequences of the budget to speak on behalf of Canada’s scientific community.

That’s the thing about federal budgets: there is only a limited amount of money to spend. I know as a taxpayer that for every dollar the government spends on research and innovation, that is a dollar that isn’t getting spent on health care or infrastructure. Not to mention that with deficit financing, I will also be the one to pay off that debt. For me, that investment is worthwhile. And I am prepared to champion that to my fellow Canadians as to why they should also feel that matters, regardless of whether or not they are a scientist themselves. How can Bill Nye, an American, speak to any of that? He doesn’t qualify for NSERC grants. He doesn’t have to worry about Canada’s deficit. He’s not looking for jobs in Canada’s oil and gas industry. He doesn’t have to worry about under-funding some other Canadian program in order to fund science.

2) Bill Nye is Not the Only Voice

Okay, I know I have come off pretty hard on Bill Nye. I don’t hate Bill Nye. He’s done a lot for promoting STEM. But science has basically had one spokesman (two if you count Neil deGrasse Tyson) for the last 25 years. That’s not a lot of diversity. There are millions of scientific voices out there. I am personally tired of hearing Bill Nye’s perspective on science. I want to hear more of Jillian Buriak’s, Bonnie Schmidt’s, or on the more famous side Jay Ingram‘s. If I am going to hear about science from an American prospective, how about Raychelle Burks? My point here is that there are a lot of different science voices that can offer insight into why investing in STEM is a great choice for Canada. Bill Nye’s isn’t one of them.

Here’s another thing: Bill Nye’s version of science communication has actually done some damage to science itself. His willingness to entertain non-scientific individuals in debates about creationism or climate change, he has given these science deniers an elevated platform that they wouldn’t normally have. It puts creationism and climate change denial on the same level as scientific fact. It suggests that their beliefs they are passing off as fact are on the same level as scientific data. After all, debates are about two perspectives on the same set of facts right? Thanks Bill, but this wasn’t helpful. Actually, it made it harder for every other scientist trying to promote scientific literacy in the fields of climate change and evolution. This Scientific American article basically explains what I am trying to get at here.

3) The Kinder Morgan Thing

Or as Bill Nye called it “Morgan Kinder“. Pipelines and oil – this is contentious. I don’t want to get into all the science about oil or its impact on the environment. Yes, we know it is bad environmentally; yes, we know it is contributing to climate change; yes, we need to regulate and fix this problem. BUT that doesn’t happen by simply turning off the pipes. (Hey Bill, how’d you get to Canada? Did you like that jet fuel keeping the plane in the air? How about that car from the airport to the University of Ottawa? Was that water bottle you were drinking from plastic?) If you’re in Alberta right now, like me, you know that there is a lot going on in respect to the Trans Mountain Pipeline. The fact that this particular issue is so contentious that British Columbia and Alberta are having to go to the federal government to solve the damn issue should probably say to anyone, especially an American outsider, that maybe this wasn’t the best venue for discussing pipelines and what they mean. (Also, where is Bill discussing American shale gas production?) I go back to my point about Bill Nye not being Canadian. The pipeline is more than a scientific issue in Canada, with stakeholders in many sectors of the Canadian economy. Bill Nye is not one of those stakeholders and his woeful ignorance about this issue’s complexity was on display.

Now, I have ranted on Twitter. I have shared my thoughts here. But none of this is really going to create that much action. I am just not that important. But I believe that by taking action we put more meaning into our words. This is why I actually wrote a letter to the Prime Minister. I doubt that I will get a response, but I couldn’t very well complain about his choice on Twitter and not write to him to share my incredible disappointment in his decision to take away a great opportunity for Canadians to meet their amazing scientists and instead give it to the tired voice of science’s mascot, Bill Nye.

*Full disclosure: I have been a supporter of the Liberal Party but my previous political support does not mean an unconditional support of all their choices. That’s the fun part about democracy.

I thought I would talk a little about pharmaceuticals. Chances are you take some, know someone who takes them, and have all complained about their prices. A few years ago while I was in grad school I took a pharmaceutical chemistry class taught by scientists from Gilead, and I must say it was very enlightening. I thought I would share some of the lessons I learned and some of the key problems that face those charged with making these chemicals that many people depend on.

Let’s start with a poignant news story. What would you do if you were suddenly unable to get a hold of a medication that you require? When a company decides to stop producing a compound, what can be done? Is that right or wrong? How should medications be priced? These are questions that are very difficult to answer.

To understand a little bit about the complexity of the issues with the pharmaceutical industry I think it is first important to understand how these medications are produced. I know I found it eye opening. Guess how long it takes to produce a drug? 0-5 yrs? 5-10 yrs? 10-15 yrs? 15-20 yrs? If you guessed 15-20 yrs, then you would be correct. It takes 20 years and (as of 2008) $1.7 billion to develop a SINGLE drug.

The timeline:

Discovery/Preclinical Trials

Time: 1-3 years

In this time, the company will begin by identifying a medical need, such as anti-HIV medications, and then study that disease to determine where drugs can target the disease and the possible interactions of the drug. This is where potential contenders for a drug are determined. This amounts to some 30 000 chemical compounds will be screened! These preclinical trials will involve pharmacodynamics and pharmacokinetics.

Pharmacodynamics: studies how a drug interacts with a target-this is the impact of the drug on the body. Is the drug going to do what is was intended to do? Is it going to do something else?

Pharmacokinetics: this is how a drug is transported to the target-this is really looking at the impact of the body on the drug. This looks at four things: absorption, distribution, metabolism, and excretion. Remember, your body is one self contained complex chemical reactor. I think one excellent example of the importance of studying this effect is the notorious thalidomide. There are two versions of thalidomide: R and S. One is an anti-emetic (R) while the other causes birth defects (S). Yes it is possible to separate the two and give a person only the version that DOES NOT cause birth defects; however, once in the body, the drug is inter-converted to the other form (a process called racemisation).

Any potential drug will be screened for toxicity using two species: one rodent and one non-rodent. They will be tested for single and repeated dosing. They will be tested by various delivery methods. (Side note: a 14-day rat trial costs $250 000.)

During this time, chemists will be answering the questions of: can the drug be made? How many steps (hint: more steps, more costly, more trouble)? What are the yields (not all chemical conversions give 100% yield-actually very few give 100%)? Is chemical manufacturing possible, feasible, and affordable?

After all of this, about 100-200 of the 30 000 compounds will make it on to the next step.

Safety Review

Time: about 30 days

This is where the pharmaceutical company is trying to get approval from human clinical trials. All of the information gleaned in the preclinical trials must be presented to the regulatory bodies, including the synthetic routes for production. This is also the time that a company will take out a patent on a compound (a process in the tens of thousands of dollars for each one).

– 50-70% of the compounds (that made it to clinical trial) will be abandoned.

Phase 2:

– 50-500 patients

– 2 years

– 60% of the compounds (that made it to phase 2) will be abandoned

Phase 3:

– 500-2000 patients

– 3-5 years

– only 4-10% of compounds will succeed

Approval:

Time: up to 7 years

This is the stage where regulatory bodies determine if a drug is safe enough and effective enough to sell to the population.

Now if you have been keeping track, we are about 15 years from when the patent was filed to the point that the drug can be sold. A patent is only good for 20 years; therefore, a company only has about 5 years to recover the cost of the production. This also means that drugs that are currently hitting the market were just getting out of preclinical trials in 1998.

During this time, optimisation is ongoing to make the manufacturing process safer, cheaper, and more efficient. However, if the process is changed too much, it may mean that a company will need to refile their drug for approval.

There is lots of interesting chemistry in pharmaceutical production. I think I will leave that for another entry, but if you have found this interesting, please check out these course notes for reference material.